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TAT peptide-modified liposomes provide enhanced gene delivery to intracranial human brain tumor xenografts in nude mice.

Abstract
In this study, we have investigated the potential of trans-activating transcriptional activator peptide (TATp)-modified liposomes to enhance the delivery of the model gene, plasmid encoding for the green fluorescent protein (pEGFP-N1), to human brain tumor U-87 MG cells in vitro and in an intracranial model in nude mice. The TATp-lipoplexes were characterized at lipid/DNA (+/-) charge ratios of 0.2, 5, 10, and 20 for size analysis and DNA complexation. The size distribution of DNA-loaded TATp-liposomes was narrow and the DNA complexation was firm at lipid/DNA (+/-) charge ratios of 5 and higher. TATp-lipoplexes had demonstrated an enhanced delivery of pEGFP-N1 to U-87 MG tumor cells in vitro at lipid/DNA (+/-) charge ratios of 5 and 10. In vivo transfection of intracranial brain tumors by intratumoral injections of TATp-lipoplexes showed an enhanced delivery of pEGFP-N1 selectively to tumor cells and subsequent effective transfection compared to plain plasmid-loaded lipoplexes. No transfection (green fluorescence of the GFP) was noted in the normal brain adjacent to tumor.
AuthorsBhawna Gupta, Tatiana S Levchenko, Vladimir P Torchilin
JournalOncology research (Oncol Res) Vol. 16 Issue 8 Pg. 351-9 ( 2007) ISSN: 0965-0407 [Print] United States
PMID17913043 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Gene Products, tat
  • Liposomes
  • Green Fluorescent Proteins
  • DNA
Topics
  • Animals
  • Astrocytoma (pathology, therapy)
  • Brain Neoplasms (pathology, therapy)
  • Cerebral Cortex
  • DNA (administration & dosage, genetics)
  • Drug Administration Routes
  • Gene Products, tat (administration & dosage)
  • Gene Transfer Techniques
  • Genes, tat (genetics)
  • Genetic Therapy (methods)
  • Green Fluorescent Proteins (genetics)
  • Humans
  • Injections, Intralesional
  • Liposomes
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Transfection
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Up-Regulation
  • Xenograft Model Antitumor Assays

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